Composition and method to whiten and exfoliate skin

ABSTRACT

A composition which is effective as a skin whitening agent is disclosed. The composition includes one or more jojoba plant parts. The composition further includes Simmondsin. A method of promoting skin whitening, comprising the step of topically administering to an individual a composition in an amount effective to whiten skin, where that composition comprises one or more parts of the jojoba plant.

FIELD OF THE INVENTION

[0001] Applicant's invention relates to a composition and method towhiten, and optionally exfoliate, skin.

BACKGROUND OF THE INVENTION

[0002] Exposure to the sun over time can induce many biochemicalreactions in the skin. For example, exposure can lead to sunburn andtanning, which are immediate and well recognized. Other consequences ofexposure to the sun are more subtle and accumulate over time. Oftenmelanocytes can accumulate and the action of the enzyme tyrosinase isincreased. These changes can result in the development of age spots andcreate an uneven, mottled skin tone. Unfortunately, many of thecommercially available products in today's market are either onlymarginally effective, or contain active agents that are unstable andlose their potency when incorporated into a final formula.

[0003] The ability to modify the expression of pigment content in theskin, to promote an even-looking skin tone and a more youthfulappearance, is highly desired in today's society. Many people desire tomodify their skin tone, to reduce aging spots, melasma, etc., or forpurely cosmetic reasons. In fact, in the Far East, a lighter skin toneis desirable and is associated with higher socio-economic status.

[0004] Hyper-pigmentation in the skin is caused by the over expressionor accumulation of melanin in the skin. As a result, the pathwayinvolved in melanin production has been the target for many inhibitorsso as to reduce the levels produced. One of the principal enzymesinvolved in the melanin pathway is tyrosinase.

[0005] Skin functions include, inter alia, protection, heat regulation,immune response, and sensory detection. With age, the skin's naturalrejuvenation process slows. In addition, skin aging many times resultsin development of not only hyperpigmentation, but alsohyperkeratinization wherein corneocytes adhere in excess causing athickening of the stratum corneum. The stratum corneum comprises aportion of the epidermis, and includes nonviable corneocytes which arecells that have lost the nucleus and cytoplasm organelles.

[0006] What is needed is a composition which can be effectively used asa topically applied skin whitening agent. In addition, it is desirableto have a topical composition which can whiten skin as well as induceshedding of dry scales from the skin's surface thereby promoting arejuvenated, fresher complexion. Applicant has now discovered acomposition comprising tyrosinase inhibitors, and/or melanin cellsynthesis inhibitors, in optional combination with skin exfoliatingagents, which is useful in topically applied cosmetic and pharmaceuticalformulations.

SUMMARY OF THE INVENTION

[0007] Applicants' invention includes a composition which is effectiveas a skin whitening agent. Applicant's composition comprises jojoba. By“jojoba,” Applicant means any portion of the jojoba plant, includingwithout limitation jojoba meal, but not including jojoba oil. In certainembodiments, Applicant's composition comprises jojoba in combinationwith jojoba oil. Applicant's composition includes Simmondsin and/orSimmondsin derivatives. Applicant's invention further includes a methodof promoting skin whitening, comprising the step of topicallyadministering to an individual a composition in an amount effective towhiten skin, where that composition comprises jojoba.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The invention will be better understood from a reading of thefollowing detailed description taken in conjunction with the drawings inwhich like reference designators are used to designate like elements,and in which:

[0009]FIG. 1 is a flow chart summarizing the steps of Applicant's methodto form his composition.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] Referring to the illustrations, like numerals correspond to likeparts depicted in the figures. The invention will be described asembodied in composition which includes jojoba meal. Applicant'sinvention, however, is not limited to use of jojoba meal. Rather,Applicant's invention includes a composition comprising one or moreparts of the jojoba plant, including but not limited to jojoba seed,pressed jojoba seed, jojoba roots, jojoba bark, jojoba leaves, andcombinations thereof. Applicant's invention further includes use ofApplicant's composition to affect the visual appearance of skin.

[0011] All patents, applications, test methods and publicationsreferenced in this specification are hereby incorporated by reference intheir entirety. In case of conflict, the present description, includingdefinitions, will prevail. The present invention is directed in part toa composition which is useful as a skin whitening agent. Specifically,the invention is directed in part to a composition comprising one ormore jojoba plant parts. Applicant's composition includes Simmondsinand/or Simmondsin derivatives. In certain embodiments, Applicant'scomposition further comprises a plurality of proteins and peptidefragments which naturally occur in the jojoba plant. By “peptidefragments,” Applicant means one or more amino acid oligomers derivedfrom the cleavage of one or more jojoba proteins. In certainembodiments, Applicant's composition further includes a plurality ofamino acids.

[0012]FIG. 1 summarizes Applicant's method to prepare his composition.Referring now to FIG. 1, in step 105 Applicant's method provides one ormore parts of the jojoba plant. Such jojoba plant parts include, withoutlimitation, seed, hulls, bark, roots, leaves, stems, and the like, butnot jojoba oil. In certain embodiments, step 105 includes providingjojoba seed. In certain embodiments, jojoba seed is provided by theDesert Whale Jojoba Company of Tucson, Ariz. Jojoba seed comprisesapproximately 50 percent jojoba oil. The various parts of the jojobaplant, including jojoba seed, further comprises a complex mixture ofjojoba oil, jojoba proteins, carbohydrates, Simmondsin, Simmondsinderivatives, and other phytochemicals. In certain embodiments,Applicant's method transitions from step 105 to step 110. In certainembodiments, Applicants' method transitions from step 105 to step 120.In certain embodiments, Applicant's method transitions from step 105 tostep 130.

[0013] In step 110, Applicant presses the jojoba plant parts of step 105to remove about 90 percent of the jojoba oil disposed in those plantparts. In certain embodiments, such mechanical pressing is performedusing an expeller apparatus. The solid material remaining after removalof jojoba oil from jojoba plant parts is sometimes referred to as“jojoba meal.” This jojoba meal comprises up to about 12 percentresidual jojoba oil in addition to a complex mixture of jojoba proteins,sugars, Simmondsin, and other phytochemicals. In certain embodiments,Applicant's method transitions from step 110 to step 120. In certainembodiments, Applicant's method transitions from step 110 to step 130.

[0014] In step 120, the jojoba meal of step 110 is extracted using oneor more non-polar compounds. By a non-polar compound, Applicant means amaterial having a dielectric constant of about 2 or less. Such non-polarcompounds include, without limitation, pentane, hexane, cyclohexane, andthe like.

[0015] In certain embodiments, step 120 further includes using supercritical CO₂ to extract the jojoba meal. Super critical carbon dioxidecomprises highly pressurized carbon dioxide. At pressures of 250 to 350times atmospheric pressure, CO₂ takes on the density of a liquid and theviscosity of a gas, making it an efficient solvent. In its pressurizedstate, CO₂ is pumped into a sealed chamber containing jojoba meal, whereit is allowed to circulate to remove the residual jojoba oil. Two of themajor advantages of CO₂ are that it does not leave a chemical residueand it has a minimal to no effect on the structure of the extractedjojoba oil.

[0016] In certain embodiments, step 120 includes extracting the pressedjojoba plant parts with one or more solvents having a dielectricconstant of about 6 or less. Such solvents include, without limitation,methyl formate, methyl acetate, ethyl acetate, ethers, and halogenatedalkyls.

[0017] In step 130, the jojoba meal is milled. In certain embodiments,the milled jojoba meal has a average particle size of 50 microns with astandard deviation of 1.83. In certain embodiments, the milled jojobameal has no particles larger than about 180 microns.

[0018] As those skilled in the art will appreciate, because Applicants'milled jojoba meal comprises a natural material harvested from anoutdoor environment, that jojoba meal may include one or moreundesirable naturally-occurring organisms, such as one or more molds andthe like. In step 140, Applicant's milled jojoba meal is sterilized. Incertain embodiments, Applicant's jojoba meal is irradiated to killundesirable organisms. In certain embodiments, Applicant's jojoba mealis exposed to chemical means to kill undesirable organisms.

[0019] In certain embodiments, such chemical means include exposing saidjojoba meal to one or more acids. In certain embodiments, those one ormore acids include one or more hydroxy acids. In certain embodiments,such chemical means comprise one or more gaseous compounds, such as forexample, ethylene oxide.

[0020] Samples of Applicant's extracted/milled jojoba meal were sent toSteris-Isomedix Services in El Paso, Tex. for sterilization with gammarays using a Nordian Cobalt-60 Irradiator #167. TABLES 1, 2, 3, and 4,summarize the results. TABLE 1 recites the detected plate counts priorto irradiation. TABLE 2 recites the detected plate counts afterirradiation with between 9 to 30 Kilograys. TABLE 3 recites the detectedplate counts after irradiation with between 30 to 50 Kilograys. TABLE 4recites the detected plate counts after irradiation with more than 50Kilograys. TABLE 1 COMPONENT ASSAY UNITS Aerobic Plate Count 46,000CFU/g Anaerobic Plate Count 160 CFU/g Mold (aerophilic) 640 CFU/g Yeast<10 CFU/g

[0021] TABLE 2 COMPONENT ASSAY UNITS Aerobic Plate Count 100 CFU/gAnaerobic Plate Count <10 CFU/g Mold (aerophilic) <10 CFU/g Yeast <10CFU/g

[0022] TABLE 3 COMPONENT ASSAY UNITS Aerobic Plate Count <100 CFU/gAnaerobic Plate Count <10 CFU/g Mold (aerophilic) <10 CFU/g Yeast <10CFU/g

[0023] TABLE 4 COMPONENT ASSAY UNITS Aerobic Plate Count <100 CFU/gAnaerobic Plate Count <10 CFU/g Mold (aerophilic) 10 CFU/g Yeast <10CFU/g

[0024] In certain embodiments, step 140 includes exposing the milledjojoba meal to between about 9 to about 30 Kilograys of gammairradiation. In certain embodiments, step 140 includes exposing themilled jojoba meal to between about 30 to about 50 Kilograys of gammairradiation. After the sterilization of step 140, milled/sterilizedjojoba meal is combined with other components to form Applicant's skinwhitening composition. In certain embodiments, Applicant's compositionincludes up to about 50 weight percent milled/sterilized jojoba meal.

[0025] In step 150, the milled/sterilized jojoba meal of step 140 isplaced in a first vessel equipped with a side-scraping mixer. In certainembodiments, step 150 further includes adding water to themilled/sterilized jojoba meal. In certain embodiments, the watercomprises deionized water. In step 160, one or more organic compoundscomprising at least one polar group are added to that first vessel. Incertain embodiments, step 160 includes adding one or more alcohols tothe milled/sterilized jojoba meal of step 140. In certain embodimentssuch one or more alcohols include, without limitation, n-butanol,sec-butanol, tert-butanol, and the like.

[0026] In certain embodiments, step 160 includes adding one or morediols to the milled/sterilized jojoba meal of step 140. In certainembodiments such one or more diols include, without limitation, ethyleneglycol, propylene glycol, polyethyleneoxide diol, polyproyleneoxidediol, and the like. In certain embodiments, step 160 includes adding oneor more polyols to the milled/sterilized jojoba meal of step 140. Incertain embodiments such one or more polyols include, withoutlimitation, glycerin, polyethyleneoxide triols, polypropyleneoxidetriols, and the like.

[0027] In certain embodiments, Applicant's method includes step 155wherein one or more acids are added to the jojoba meal. In certainembodiments, the one or more acids of step 155 include, for example,formic acid, acetic acid, propionic acid, and the like. In certainembodiments, steps 150, 155, and 160, comprise mixing milled/sterilizedjojoba plant parts with n-butanol and formic acid. In certain of theseembodiments, an n-butanol and 1-normal formic acid mixture comprisingabout a 92:8 volume/volume ratio is used, and the jojobameal/butanol/formic acid mixture is stirred for about 30 minutes.

[0028] In certain embodiments, the one or more acids of step 155comprise one or more hydroxy-acids. By “hydroxy-acid,” Applicant means acompound having a carboxylic acid functionality and a hydroxyfunctionality. In certain embodiments, the one or more hydroxy-acids ofstep 155 include one or more alpha-hydroxy acids. Such alpha-hydroxyacids include, without limitation, glycolic acid, lactic acid, mandelicacid, malic acid, citric acid, tartaric acid, and combinations thereof.In certain embodiments, the one or more acids of step 155 include one ormore beta-hydroxy acids, such as and without limitation, salicylic acid,beta hydroxybutanoic acid, tropic acid, trethocanic acid, and the like,and mixtures thereof. In certain embodiments, the one or more acids ofstep 155 include one or more alpha hydroxy acids in combination with oneor more beta-hydroxy acids.

[0029] Embodiments of Applicant's method that comprise adding one ormore hydroxy acids in step 155, form compositions that have both skinwhitening and skin exfoliation properties. For example, topicalapplication of one or more alpha-hydroxy acids, and/or one or morebeta-hydroxy acids, promotes dissolution of adhesions between cells inthe upper layers of the skin. Such topical application of one or morehydroxy acids results in shedding dry scales from the skin, i.e.exfoliation. Such exfoliation stimulates the growth of new skin therebyproviding a rejuvenated, fresher complexion.

[0030] In step 170, deionized water is placed in a second vessel. Incertain embodiments Applicant's method includes step 175. In step 175,Applicant's method adds one or more water-soluble, basic compounds tothe second vessel. By “water-soluble, basic compound,” Applicant mean amaterial which when dissolved in water produces an aqueous mixturehaving a pH greater than 7.0. In certain embodiments, the one or morebasic compounds of step 155 include NH₄OH, NaOH, KOH, sodium acetate,potassium acetate, sodium benzoate, potassium benzoate, and the like. Incertain embodiments, the one or more basic compounds comprise polymericmaterials. For example, in certain embodiments step 175 includes addingpolyethyleneimine to the second vessel. In certain embodimentsApplicant's method transitions from step 175 to step 180. In otherembodiments, Applicant's method transitions from step 170 to step 180.

[0031] In step 180, one or more thickening agents is added to the secondvessel. In certain embodiments, the one or more thickening agents ofstep 180 include one or more water-soluble polymers. In certainembodiments, those one or more water-soluble polymers include one ormore cationic polymers. In certain embodiments, the one or more cationicpolymers include guar hydroxypropyltrimonium chloride. In certainembodiments, the one or more cationic polymers include cationichydroxyethylcellulose. In certain embodiments, the one or more cationicpolymers includes salts of polyethyleneimine, polyvinylpyridine,poly-2-ethyl-2-oxazoline, and the like. In certain embodiments, the oneor more cationic polymers have a charge density of between about 0.40meq/g and about 1.2 meq/g.

[0032] In step 190, the mixture of step 160 is added to the stirredmixture of step 180 to form Applicant's composition. The composition isstirred until a uniform consistency is formed. In certain embodiments,the mixture of step 190 is stirred for at least 30 minutes.

[0033] In certain embodiments, steps 150, 155, and 160, comprise mixingmilled/sterilized jojoba meal with n-butanol and formic acid, and steps170 and 175 comprise forming an aqueous alkaline solution using, forexample, NaOH, and. In these embodiments, the pH of the mixture of step190 is initially adjusted to be about 10, and after stirring for about30 minutes the pH is then lowered to about 7. In these embodiments, thecomposition of step 195 includes an aqueous component comprisingdissolved Simmondsin/Simmondsin derivatives and a plurality of dissolvedjojoba proteins, in combination with a heterogeneous jojoba mealcomponent.

[0034] In certain embodiments, the Applicant's composition has a pH ofabout 3. In certain embodiments, the Applicant's composition has a pH ofabout 4. In certain embodiments, the Applicant's composition has a pH ofabout 5. In certain embodiments, the Applicant's composition has a pH ofabout 6. In certain embodiments, the Applicant's composition has a pH ofabout 7. In certain embodiments, the Applicant's composition has a pHbetween 7 and 8.

[0035] The embodiments of Applicants' method recited in FIG. 1 may beimplemented separately. Moreover, in certain embodiments, individualsteps recited in FIG. 1 may be combined, eliminated, or reordered. Forexample, certain embodiments of Applicant's method include steps 105,130, 140, 150, 160, 170, 180, 190, and 195. Other embodiments ofApplicant's method include steps 105, 120, 130, 140, 150, 160, 170, 180,190, and 195. Other embodiments of Applicant's method includes steps105, 110, 120, 130, 140, 150, 160, 170, 180, 190, and 195. Otherembodiments of Applicant's method includes steps 105, 110, 120, 130,140, 150, 155, 160, 170, 180, 190, and 195. Other embodiments ofApplicant's method includes steps 105, 110, 120, 130, 140, 150, 160,170, 175, 180, 190, and 195. Other embodiments of Applicant's methodincludes steps 105, 110, 120, 130, 140, 150, 155, 160, 170, 175, 180,190, and 195.

[0036] Examples I and II are presented to further illustrate to personsskilled in the art how to make and use the invention and to identifycertain embodiments thereof. These examples are not intended aslimitations, however, upon the scope of the invention, which is definedonly by the appended claims.

EXAMPLE I

[0037] The components of TABLE 5A were mixed in a first vessel. Thecomponents of TABLE 5B were mixed in a second vessel. The components ofthe first vessel were added to the second vessel with stirring to formone embodiment of Applicant's composition. TABLE 5A COMPONENT WEIGHTPERCENT Deionized Water 48 Guar Hydroxypropyltrimonium Chloride* 1

[0038] TABLE 5B COMPONENT WEIGHT PERCENT Milled/Sterilized Jojoba Meal25 Glycerin 10 Ethoxy Diglycol 10 Propylene Glycol 5 Preservative* 1

EXAMPLE II

[0039] The components of TABLE 6A were mixed in a first vessel equippedwith side scraping by first adding the water and then the jojoba meal.That mixture was stirred until uniform.

[0040] In a second vessel, the glycolic acid and lactic acid were firstadded to the water component with stirring. Thereafter, the sodiumhydroxide was slowly added. The mixture of Table 6B was added to thefirst vessel with mixing. After the addition was complete, the mixturewas heated to about 75° C. to about 80° C. with mixing for about tenminutes. During this ten minute period, the viscosity of the mixtureincreases. After holding the mixture at between about 75° C. and about80° C. for about ten minutes, the mixture was cooled to between about45° C. and about 50° C.

[0041] The components of TABLE 6C were mixed in a third vessel untiluniform. That uniform mixture of TABLE 6C was then added to the heated,and stirred mixture formed using the components of TABLES 6A and 6B toprepare this embodiment of Applicants' composition. This embodiment ofApplicant's composition was mixed until uniform and then cooled. The pHof this embodiment of Applicant's composition is between about 4 andabout 4.5. TABLE 6A COMPONENT WEIGHT PERCENT Deionized Water 36.8Milled/Sterilized Jojoba Meal 25

[0042] TABLE 6B COMPONENT WEIGHT PERCENT Deionized Water 8 Glycolic Acid(70%) 4 Lactic Acid (88%) 1.2 Sodium Hydroxide (50%) 2.8

[0043] TABLE 6C COMPONENT WEIGHT PERCENT Glycerin 8 Transcutol CG 8Propylene Glycol 4 Guar Hydroxypropyltrimonium Chloride 1 Phenobact 1Fragrance 0.2

[0044] Applicant's composition includes a plurality of jojoba proteinsand amino acids. TABLE 7 recites the amino-acid composition of theextracted jojoba meal of step 120. TABLE 7 AMINO ACID WEIGHT PERCENTLysine 1.45 Histidine 0.61 Arginine 1.95 Aspartic Acid 2.82 Threonine1.41 Serine 1.53 Glutamic Acid 3.36 Proline 1.44 Glycine 2.45 Alanine1.19 Valine 1.54 Methionine 0.35 Isoleucine 1.03 Leucine 2.02 Tyrosine1.07 Phenylalanine 1.23 Cystine 0.8 Tryptophan 0.32 TOTAL 26.57

[0045] Thus, Applicant's composition includes the amino acids recited inTABLE 7. In certain embodiments, Applicant's composition comprisesbetween about 1 and about 15 weight percent amino acids.

[0046] In addition, the extracted jojoba meal of step 120 furtherincludes Simmondsin and/or a mixture of Simmondsin derivatives and/orjojoba oil. TABLE 8 recites the reported weight percents ofSimmondsin/Simmondsin derivatives and jojoba oil in other jojoba plantparts. TABLE 8 WEIGHT WEIGHT PERCENT PERCENT PLANT PART SIMMONDSINJOJOBA OIL Core wood 0.45 — Leaves 0.19 2.0 Twigs 0.63 1.1

[0047] Jaime Wisniak, The Chemistry and Technology of Jojoba Oil,America Oil Chemists' Society, at page 223.

[0048] Applicant's composition includes Simmondsin and/or a mixture ofSimmondsin derivatives. In certain embodiments, theSimmondsin/Simmondsin derivative component comprises theSimmondsin/Simmondsin derivatives disposed in the jojoba plant parts ofstep 105 (FIG. 1). The extracted jojoba plant parts of step 120 compriseup to about 6 weight percent Simmondsin/Simmondsin derivatives. Incertain embodiments, Applicant's method includes adding additionalamounts of Simmondsin/Simmondsin derivatives. In certain embodiments,Applicant's composition comprises between about 0.01 weight percent andabout 25 weight percent Simmondsin and/or a mixture of Simmondsinderivatives. By Simmondsin, Applicant means Compound I wherein R2 ishydrogen, R3 is OH, R4 is OCH₃ and R5 is OCH₃. By Simmondsin derivative,Applicant means Compound I wherein R2 is other than hydrogen, R3 isother than OH, R4 is other than OCH₃, and R5 is other than OCH₃.

[0049] In certain embodiments, the R2 moiety of Compound I comprises aFerulic acid moiety comprising compound II.

[0050] TABLE 9 summarizes certain embodiments of Simmondsin and/orSimmondsin derivatives that are found in Applicant's composition. TABLE9 Com- pound R2 R3 R4 R5 Name III H OH OCH₃ OCH₃ Simmondsin IV H OH OHOCH₃ 4-Demethyl- simmondsin V H OH OCH₃ H 5-Demethyl- simmondsin VI H OHOH OH Didemethyl- simmondsin VII Com- OH OCH₃ OCH₃ Simmondsin pound2′-trans- II ferulate VIII OH Com- OCH₃ OCH₃ Simmondsin pound 3′-trans-II ferulate IX Com- OH OH OCH₃ 4-Demethyl- pound simmondsin II 2′-trans-ferulate X Com- OH OCH₃ OH 5-Demethyl- pound simmondsin II 2′-trans-ferulate XI Com- OH OH OH Didemethyl- pound simmondsin II trans-ferulate

[0051] In certain embodiments, Applicant's composition comprises jojobaoil. In certain embodiments, the jojoba oil component comprises part orall of the residual jojoba oil in the starting pressed jojoba meal. Inother embodiments, additional jojoba oil is added to Applicant'scomposition. Jojoba oil is obtained from the seed of the shrubSimmondsiachinensis which is native to the Sonoran desert. Jojoba oil isa mixture of naturally-occurring compounds obtained from the jojobaseed, sometimes called the jojoba bean. Jojoba seed contains about 50weight percent of a yellow oil commonly referred to as jojoba oil. Incontrast to other vegetable oils which comprise a mixture oftriglycerides, jojoba oil comprises a mixture of long-chain esters.

[0052] As those skilled in the art will appreciate, carboxylic ester XVcan be formed by the reaction of alcohol XIV and carboxylic acid XIII.In addition, an ester-group-containing compound, such as many of theconstituents of jojoba oil, can be described as comprising an R5component and an R6 component.

[0053] Jojoba oil includes a variety of ester-group-containing compoundswherein the R7 component comprises a mixture of carbon-containingmoieties having, primarily, 17, 18, 20, and 22 carbon atoms, and whereinthe R6 component comprises a mixture of carbon-containing moietieshaving, primarily, 19, 20, 22, and 24 carbon atoms. Furthermore, it isknown that the R7 component of these various jojoba oilester-group-containing constituents includes at least one carbon-carbondouble bond having a cis-configuration. Sometimes such acis-configuration is known as the Z-configuration. It is further knownthat the R6 component of these various jojoba oil ester-group-containingconstituents includes at least one carbon-carbon double bond having acis-configuration. Sometimes such a cis-configuration is known as theZ-configuration.

[0054] By “jojoba oil,” Applicant means naturally-occurring jojoba oiland/or one or more derivatives of naturally-occurring jojoba oil.Certain derivatives ofjojoba oil are known in the art. For example,isomerization of the double bond in the R7 component, and/or the R6component, of the various jojoba esters from the cis configuration to atrans configuration yields a material that is solid at room temperature,where that solid material includes one or more crystalline compounds.U.S. Pat. No. 4,329,298 teaches a method to isomerize jojoba oil and ishereby incorporated herein by reference.

[0055] In addition, hydrogenation of the double bond in the R7component, and/or hydrogenation of the double bond in the R6 component,of the jojoba oil ester yields a crystalline, wax-like material.Substantially fully hydrogenated jojoba oil is a solid with a meltingpoint upwards of 70° C. As those skilled in the art will appreciate, thedegree of hydrogenation can be measured using an Iodine Value (“IV”).Naturally-occurring jojoba oil has an IV of between about 80 and 85. Asthe percentage of carbon-carbon double bonds hydrogenated increases, theIV of that hydrogenated material decreases. As the percentage ofcarbon-carbon double bonds hydrogenated increases, the degree ofcrystallinity and the melting point of that hydrogenated material alsoincrease.

[0056] In certain embodiments, Applicant's composition comprises betweenabout 0.05 weight percent and about 90 weight percent jojoba oil. Byjojoba oil, Applicant means a naturally-occurring mixture of estercompounds obtain from jojoba seed, isomerized jojoba oil, partially orfully hydrogenated jojoba oil, and mixtures thereof. In certainembodiments, Applicant's composition includes a plurality of particlescomprising fully hydrogenated jojoba oil.

[0057] In certain embodiments, Applicant's composition further comprisesa plurality of carbohydrate compounds. In certain embodiments,Applicant's composition comprises one or more monosaccharides, one ormore disaccharides, and one or more complex saccharides.

[0058] In certain embodiments, Applicant's composition comprisesfructose. In certain embodiments, Applicant's composition comprisesfructose in a weight percentage of between about 0.50 and about 5.0. Incertain embodiments, Applicant's composition comprises glucose. Incertain embodiments, Applicant's composition comprises glucose in aweight percentage of between about 0.25 and about 2.5. In certainembodiments, Applicant's composition comprises sucrose. In certainembodiments Applicant's composition comprises sucrose in a weightpercentage of between about 0.10 and about 1.0. In certain embodiments,Applicant's composition comprises raffinose, i.e. a trisaccharide. Incertain embodiments, Applicant's composition comprises raffinose in aweight percentage of between about 0.05 and about 0.50.

[0059] In certain embodiments, Applicant's composition includes Lysineat a weight percent between about 0.01 and about 1, Histidine at aweight percent between about 0.01 and about 0.3, Arginine at a weightpercent between about 0.01 and about 1, Aspartic Acid at a weightpercent between about 0.05 and about 1.50, Threonine at a weight percentbetween about 0.01 and about 0.75, Serine at a weight percent betweenabout 0.01 and about 0.8, Glutamic Acid at a weight percent betweenabout 0.10 and about 1.75, Proline at a weight percent between about0.01 and about 0.75, Glycine at a weight percent between about 0.05 andabout 1.25, Alanine at a weight percent between about 0.05 and about0.60, Valine at a weight percent between about 0.01 and about 0.77,Methionine at a weight percent between about 0.01 and about 0.25,Isoleucine at a weight percent between about 0.01 and about 0.54,Leucine at a weight percent between about 0.05 and about 1, Tyrosine ata weight percent between about 0.01 and about 0.53, Phenylalanine at aweight percent between about 0.05 and about 0.62, Cystine at a weightpercent between about 0.01 and about 0.40, Tryptophan at a weightpercent between about 0.01 and about 0.16, Simmondsin at a weightpercent between about 0.01 and about 5, Fructose at a weight percentbetween about 0.01 and about 5, Glucose at a weight percent betweenabout 0.01 and about 5, Sucrose at a weight percent between about 0.01and about 1, and water at a weight percent between about 30 and about98.

[0060] Pending application having Ser. No. 10/236,362, assigned to thecommon assignee hereof and hereby incorporated herein, describes twoaqueous extracts of jojoba meal identified hereinafter as “Extract A”and “Extract B.” TABLE 10 recites information generated in testing thetyrosinase activity inhibition shown by Extract A and Extract B. ExtractA comprises Simmondsin/Simmondsin derivatives in an amount of about 2.36weight percent. Extract B comprises Simmondsin/Simmondsin derivatives inan amount of about 0.44 weight percent.

[0061] Test solutions using mouse melanoma cells B16F10 were prepared,and 50 micromoles of Extract A or Extract B, along with L-DOPA at0.025%, were added to those test solutions. The test solutions wereincubated from about 1 hour to about 3 hours. The melanin content of thetest solutions were measured before and after incubation using photoabsorption methods. The tyrosinase activities recited in TABLE 10 weredetermined using those melanin values. TABLE 10 Tyrosinase TyrosinaseActivity (%) Activity (%) Concentration, measured using measured usingv/v % Extract A Extract B 0 100 110 0.02 97 104.3 0.05 95.2 103.7 0.189.1 105.2 0.3 77.1 102.6 0.6 56 98.3 1.2 10.4 78.3 2.5 −3.1 52.7

[0062] The data recited in TABLE 10, above, indicate that topicalapplication of Applicant's composition will cause a skin whiteningeffect.

[0063] TABLE 11 recites information generated in testing the tyrosinaseactivity inhibition shown by Extract A and Extract B. Test solutionsusing human melanocyte cells NHEM were prepared, and 50 micromoles ofExtract A or Extract B, along with L-DOPA at 0.025%, were added to thosetest solutions. The test solutions were incubated from about 1 hour toabout 3 hours. The tyrosinase activities of the test solutions weremeasured before and after incubation using photo absorption methods.TABLE 11 Tyrosinase Tyrosinase Activity (%) Activity (%) Concentration,measured using measured using v/v % Extract A Extract B 0 100 100 0.0299 101.2 0.05 94.6 98.3 0.1 92.7 97.8 0.3 78.6 91.8 0.6 56.7 85.7 1.239.2 69.4 2.5 1.2 29.5

[0064] The data of TABLE 11 indicate that topical application ofApplicant's composition will cause a skin whitening effect.

[0065] TABLE 12 recites data relating to the melanin content of mouseB16F10 melanoma cells in the presence of various concentrations ofExtract A and various concentrations of Extract B. Mouse B16F10 melanomacells were prepared on a plate with about 2,000 cells in Dulbecco'sModified Eagle Medium with 5% v/v Fetal Bovine Serum. Those cells werecultured. A specific concentration of either Extract A or Extract B wasadded, and the test sample cultured for 6 days. Thereafter, the cellswere washed out off the plates with Phosphate Buffer Saline Solution,and cell pellets were prepared. The color of each cell pellet wasdetermined, and classified between 5 (black) to 1 (white) with 0 meaningnot detectable. The protein content of each cell pellet was thendetermined, and the total melanin content in micrograms was calculatedper microgram of protein. A Negative Control experiment was performedwherein no skin whitening agent was added to the cells. Positive Controlexperiments were performed wherein Sodium lactate was added to testcultures at either a 25 mM level or a 50 mM level. TABLE 12Concentration Negative Positive Extract Extract v/v % Control Control AB 0.2 0.543 0.169 0.344 0.5 0.543 0.240 0.194 0.322 1.0 0.543 0.1070.187 0.213

[0066] The data of TABLE 12 indicate that Applicant believes thattopical application of his composition will cause a skin whiteningeffect.

[0067] TABLE 13 recites the observed Vidjual color determinations forthe cell pellets. A Vidjual score of 5 means the cell pellet was black.A Vidjual score of 1 means the cell pellet was white. A Vidjual score of0 means the cell pellet was not detectable, i.e. it has no color at all.TABLE 13 Concentration Negative Positive Extract Extract v/v % ControlControl A B 0.2 5 3 4 0.5 5 3 3 4 1.0 5 1 0 0

[0068] The data of TABLE 13 indicate that topical application ofApplicant's composition will cause skin whitening effects.

[0069] Applicant's extracted, milled, and irradiated, jojoba meal wastested for in vitro dermal irritancy potential using an observed ET-50test wherein normal, human-derived epidermal keratinocytes, whichclosely parallel human skin, were treated with a 20% w/w mixture ofApplicant's extracted/milled/irradiated jojoba meal in water. Six (6)well plates containing the dosed EpiDerm samples were incubated at 37°C., 5% CO₂, and greater than 90% humidity. After the appropriateexposure periods, each insert was individually removed from its plateand rinsed with a phosphate buffered saline solution to remove anyresidual material. Each insert was then rinsed a second time, excessliquid was shaken off, the EpiDerm sample was placed into 300microliters of {3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazoliumbromide} (“MTT”), and the sample was then returned to the incubator.

[0070] After three hours of MTT exposure, each insert was removed andagain rinsed to remove any residual MTT solution. The inserts were thenplaced into one well of a 24 well extraction plate. Each insert was thenimmersed in two milliliters of extraction solution overnight. After theexposure, a 200 microliter aliquot of each extract was removed forevaluation. A Dynatech MR 3000 Automatic Plate Reader was used todetermine the absorbance of each extract at 570 nm. With the absorbanceof a negative control defined as 100%, the percent absorbances of thetest articles were determined. The percentage recited in TABLE 14directly correlate with the cell metabolism in the EpiDerm samples.TABLE 14 EXPOSURE PERCENT PERCENT PERIOD VIABILITY INHIBITION 1 Hour 106−6 4.5 Hour   80 20 20 Hour  85 15

[0071] A semi-log scale was used to plot the percent viabilities on thelinear y axis against the dosing times on the log x axis. Byinterpolation the time at which the percent viability would be 50%, i.e.an “ET-50” time, was estimated. Applicant's extracted, milled,irradiated, jojoba meal showed an ET-50 value greater than 24 hours.Such an ET-50 value corresponds to a “Non-Irritating” category.

[0072] In certain embodiments, Applicant's composition further includesa cosmetically acceptable carrier and/or a pharmaceutically acceptablecarrier. By “cosmetically acceptable” and “pharmaceutically acceptable,”Applicant means those drugs, medicaments, or inert ingredients which aresuitable for use in contact with the tissues of humans and lower animalswithout undue toxicity, incompatibility, instability, irritation, andthe like, commensurate with a reasonable benefit/risk ratio. In certainembodiments, the cosmetically acceptable vehicle will form from about 1weight percent to about 99.9 weight percent of Applicant's composition.In certain embodiments, the cosmetically acceptable vehicle comprisesbetween about 50 weight percent and about 99 weight percent ofApplicant's composition. In certain embodiments, Applicant's compositioncomprises a cream, an ointment, a foam, a lotion, a plaster, or anemulsion.

[0073] One or more embodiments of Applicant's composition may beincluded in a wide variety of personal care products. Such personal careproducts include, without limitation, skin exfoliation products, skinmoisturizers, massage oils, soaps, sunscreens, skin cleaners, and thelike.

[0074] The present invention contemplates a method of visibly whiteninghuman skin comprising applying to the skin a composition containing ajojoba extract wherein the composition is applied in an amount and for aperiod of time sufficient to visibly whiten the skin. In certainembodiments, the composition is topically applied to darkened skin areasin a predetermined or as-needed regimen either at intervals byapplication of a lotion or the like, it generally being the case thatgradual lightening is noted with each successive application. Insofar asApplicant has determined, based upon in vitro testing, no adverse sideeffects will likely be encountered upon repetitive use of Applicant'scomposition.

[0075] While the preferred embodiments of the present invention havebeen illustrated in detail, it should be apparent that modifications andadaptations to those embodiments may occur to one skilled in the artwithout departing from the scope of the present invention as set forthin the following claims.

I claim:
 1. A composition which is effective as a skin whitening agent,said composition comprising one or more parts of the jojoba plant. 2.The composition of claim 1, further comprising Simmondsin.
 3. Thecomposition of claim 2, wherein said Simmondsin is selected from thegroup consisting of Simmondsin, 4-Demethylsimmondsin,5-Demethylsimmondsin, Didemethylsimmondsin, Simmondsin2′-trans-ferulate, Simmondsin 3′-trans-ferulate, 4-Demethylsimmondsin2′-trans-ferulate, 5-Demethylsimmondsin 2′-trans-ferulate,Didemethylsimmondsin trans-ferulate, and mixtures thereof.
 4. Thecomposition of claim 2, further comprising a Ferulic acid moiety.
 5. Thecomposition of claim 2, further comprising: a plurality of jojobaproteins; and one or more carbohydrates.
 6. The composition of claim 5,wherein said one or more carbohydrates comprise: one or moremonosaccharides; one or more disaccharides; and one or moretrisaccharides.
 7. The composition of claim 6, further comprising:glucose; fructose; and sucrose.
 8. The composition of claim 7, furthercomprising raffinose.
 9. A composition which is effective as a skinwhitening agent, said composition comprising: Lysine at a weight percentbetween about 0.01 and about 1; Histidine at a weight percent betweenabout 0.01 and about 0.3; Arginine at a weight percent between about0.01 and about 1; Aspartic Acid at a weight percent between about 0.05and about 1.50; Threonine at a weight percent between about 0.01 andabout 0.75; Serine at a weight percent between about 0.01 and about 0.8;Glutamic Acid at a weight percent between about 0.10 and about 1.75;Proline at a weight percent between about 0.01 and about 0.75; Glycineat a weight percent between about 0.05 and about 1.25, Alanine at aweight percent between about 0.05 and about 0.60; Valine at a weightpercent between about 0.01 and about 0.77, Methionine at a weightpercent between about 0.01 and about 0.25; Isoleucine at a weightpercent between about 0.01 and about 0.54; Leucine at a weight percentbetween about 0.05 and about 1; Tyrosine at a weight percent betweenabout 0.01 and about 0.53; Phenylalanine at a weight percent betweenabout 0.05 and about 0.62; Cystine at a weight percent between about0.01 and about 0.40; Tryptophan at a weight percent between about 0.01and about 0.16; Simmondsin at a weight percent between about 0.01 andabout 5; Fructose at a weight percent between about 0.01 and about 5;Glucose at a weight percent between about 0.01 and about 5; Sucrose at aweight percent between about 0.01 and about 1; and water at a weightpercent between about 30 and about
 98. 10. A composition which iseffective as a skin whitening agent and a skin exfoliation agent, saidcomposition comprising: one or more parts of the jojoba plant; and oneor more hydroxy acids.
 11. The composition of claim 10, wherein said oneor more hydroxy acids are selected from the group consisting of one ormore alpha-hydroxy acids, one or more beat-hydroxy acids, andcombinations thereof.
 12. The composition of claim 10, wherein said oneor more parts of the jojoba plant comprise Simmondsin, said compositionfurther comprising a Ferulic acid moiety.
 13. The composition of claim12, wherein said Simmondsin is selected from the group consisting ofSimmondsin, 4-Demethylsimmondsin, 5-Demethylsimmondsin,Didemethylsimmondsin, Simmondsin 2′-trans-ferulate, Simmondsin3′-trans-ferulate, 4-Demethylsimmondsin 2′-trans-ferulate,5-Demethylsimmondsin 2′-trans-ferulate, Didemethylsimmondsintrans-ferulate, and mixtures thereof.
 14. The composition of claim 12,further comprising: a plurality ofjojoba proteins; and one or morecarbohydrates.
 15. The composition of claim 14, wherein said one or morecarbohydrates comprise: one or more monosaccharides; one or moredisaccharides; and one or more trisaccharides.
 16. A composition fortopical use, comprising one or more parts of the jojoba plant, whereinsaid composition inhibits melanin synthesis.
 17. The composition ofclaim 16, further comprising a preparation selected from the groupconsisting of a cream, an ointment, a foam, a lotion, a plaster, and anemulsion.
 18. A composition for topical use, comprising one or moreparts of the jojoba plant, wherein said composition inhibits tyrosinaseactivity.
 19. The composition of claim 18, further comprising apreparation selected from the group consisting of a cream, an ointment,a foam, a lotion, a plaster, and an emulsion.
 20. A method of promotingskin whitening, comprising the step of topically administering to anindividual a composition in an amount effective to whiten skin, whereinsaid composition comprises one or more parts of the jojoba plant. 21.The method of claim 20, wherein said composition comprises thecomposition of claim
 2. 22. The method of claim 19, further comprisingrepeating the topical administration of said composition as required foreffectiveness.
 23. A method of promoting skin whitening and skinexfoliation, comprising the step of topically administering to anindividual a composition in an amount effective to whiten and exfoliateskin, wherein said composition comprises one or more parts of the jojobaplant and one or more hydroxy acids.
 24. The method of claim 23, whereinsaid one or more hydroxy acids are selected from the group consisting ofone or more alpha-hydroxy acids, one or more beta-hydroxy acids, andcombinations thereof.
 25. The method of claim 23, wherein saidcomposition comprises the composition of claim
 10. 26. The method ofclaim 23, further comprising repeating the topical administration ofsaid composition as required for effectiveness.
 27. A method to form askin whitening composition, comprising the steps of: providing one ormore jojoba plant parts; milling said one or more jojoba plant parts;adding one or more organic compounds comprising a polar group to saidmilled and sterilized one or more jojoba plant parts to form said skinwhitening composition.
 28. The method of claim 27, further comprisingthe step of: sterilizing said one or more jojoba plant parts.
 29. Themethod of claim 27, further comprising the step of extracting said oneor more jojoba plant parts with one or more solvents having a dielectricconstant of about 6 or less.
 30. A method for whitening human skincomprising topically applying an effective amount of a compositionproduced by the method of claim
 27. 31. A method to form a skinwhitening and exfoliation composition, comprising the steps of:providing one or more jojoba plant parts; milling said one or morejojoba plant parts; forming a mixture comprising said milled andsterilized one or more jojoba plant parts, one or more organic compoundscomprising a polar group, and one or more hydroxy acids.
 32. The methodof claim 31, wherein said one or more hydroxy acids are selected fromthe group consisting of one or more alpha-hydroxy acids, one or morebeta-hydroxy acids, and combinations thereof.
 33. The method of claim31, further comprising the step of: extracting said one or more jojobaplant parts with one or more compounds having a dielectric constant ofabout 6 or less prior to milling.
 34. The method of claim 33, whereinsaid one or more solvents having a dielectric constant of about 6 orless comprises super critical carbon dioxide.
 35. A method for whiteningand exfoliating human skin comprising topically applying an effectiveamount of a composition produced by the method of claim 31.